DE19834007C1 - Estradiol-containing patch for the transdermal application of hormones and its use - Google Patents
Estradiol-containing patch for the transdermal application of hormones and its useInfo
- Publication number
- DE19834007C1 DE19834007C1 DE19834007A DE19834007A DE19834007C1 DE 19834007 C1 DE19834007 C1 DE 19834007C1 DE 19834007 A DE19834007 A DE 19834007A DE 19834007 A DE19834007 A DE 19834007A DE 19834007 C1 DE19834007 C1 DE 19834007C1
- Authority
- DE
- Germany
- Prior art keywords
- active substance
- containing patch
- reservoir
- patch
- estradiol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0208—Tissues; Wipes; Patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/65—Characterized by the composition of the particulate/core
- A61K2800/651—The particulate/core comprising inorganic material
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Birds (AREA)
- Dermatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
Description
Die Erfindung betrifft ein wirkstoffhaltiges Pflaster zur kontrollierten Abgabe von Estradiol oder seinen pharmazeu tisch unbedenklichen Derivaten allein oder in Kombination mit Gestagenen an die menschliche oder tierische Haut.The invention relates to an active substance-containing plaster for controlled release of estradiol or its pharmazeu table-safe derivatives alone or in combination with gestagens on human or animal skin.
Oestrogen- und/oder gestagenhaltige Pflaster sind bereits bekannt. Sie weisen jedoch die Nachteile auf, daß sie ent weder Ethanol enthalten oder die potentielle Gefahr bergen, daß der Wirkstoff im Laufe der Zeit rekristallisiert.Patches containing estrogen and / or gestagen are already there known. However, they have the disadvantages that they ent neither contain ethanol nor pose the potential danger, that the active ingredient recrystallizes over time.
Aus der DE-OS 32 05 258 und der EP 0 285 563 ist bekannt, Estradiol und Ethanol gleichzeitig in einer Pflasterformu lierung zu verabreichen. Die Herstellung dieses Pflasters ist jedoch sehr aufwendig und der Tragekomfort nach Appli kation aufgrund der fehlenden Flexibilität gering.It is known from DE-OS 32 05 258 and EP 0 285 563 Estradiol and ethanol at the same time in one patch administration. The production of this patch is very expensive and the comfort according to Appli cation due to the lack of flexibility.
Die EP 0 285 563 beschreibt ein transdermales therapeuti sches System für die kombinierte Applikation von Oestroge nen und Gestagenen. Das Reservoir erhält die Wirkstofffor mulierung und gegebenenfalls eine Membran sowie Ethanol als perkutanes absorptionsverbesserndes Mittel. Da die Freiset zung des Wirkstoffs hauptsächlich von der Membran gesteuert wird, unterscheidet sich dieses transdermale therapeutische System grundsätzlich von dem Wirkstoffpflaster gemäß der vorliegenden Erfindung. Der Kleber hat bei dem dort be schriebenen Pflaster lediglich die Funktion, das Pflaster auf der Haut zu befestigen. Daß er einen Beitrag zur Steue rung der Wirkstofffreisetzung zu leisten vermag, ist nicht seine Hauptaufgabe, sondern lediglich ein - möglicherweise sogar unerwünschter - Nebeneffekt. Es handelt sich hierbei um ein sogenanntes "Beutelpflaster", da sich die Wirkstoff zubereitung in einem Beutel, bestehend aus undurchlässiger Rückschicht und Membran mit Kleberschicht befindet. Infolge seines komplizierten Aufbaues ist die Herstellung des Pfla sters sehr aufwendig, da die Einzelkomponenten separat her gestellt und dann in einem weiteren Arbeitsgang zu einem Pflaster zusammengefügt werden müssen.EP 0 285 563 describes a transdermal therapeuti system for the combined application of Oestroge and gestagens. The reservoir receives the active ingredient form mulation and optionally a membrane and ethanol as percutaneous absorption enhancing agent. Because the freeset tion of the active ingredient mainly controlled by the membrane this transdermal therapeutic differs System basically from the active substance patch according to the present invention. The adhesive has been there written plaster only the function, the plaster to attach to the skin. That he made a contribution to tax It is not possible to release the active ingredient his main job, but just one - possibly even undesirable - side effect. It is this a so-called "pouch" because the active ingredient preparation in a bag consisting of impermeable Backing layer and membrane with adhesive layer is located. As a result its complicated structure is the production of the Pfla sters very complex because the individual components are made separately posed and then in a further operation to a Plasters must be put together.
Die EP 0 275 716 beschreibt ein - im Gegensatz zu dem er findungsgemäßen einschichtigen System - zweischichtiges transdermales System zur simultanen Verabreichung von einem oder mehreren Oestrogenen, die in der Polymerschicht gelöst oder mikrodispergiert sind. Die Haftschicht enthält dabei außer den Wirkstoffen Substanzen, die die transdermale Ab sorption verbessern. Polymer- und Haftschichten können aus Polyacrylaten, Silikonen oder Polyisobutylenen bestehen.EP 0 275 716 describes a - in contrast to that he inventive one-layer system - two-layer transdermal system for the simultaneous administration of one or several estrogens dissolved in the polymer layer or are microdispersed. The adhesive layer contains in addition to the active substances, substances that transdermal Ab improve sorption. Polymer and adhesive layers can be made from Polyacrylates, silicones or polyisobutylenes exist.
Die EP 0 328 806 beschreibt ein membranfreies transdermales therapeutisches System, dessen Matrix aus einem Polyacry latkleber, einem Lösemittel, einem Penetrationsverbesserer und Oestrogenen, dessen Derivaten und Kombinationen davon besteht.EP 0 328 806 describes a membrane-free transdermal therapeutic system, the matrix of which is made of a polyacrylic lat adhesive, a solvent, a penetration enhancer and estrogens, their derivatives and combinations thereof consists.
In der WO 87/07138 ist ein Estradiol-Pflaster mit einer Rückschicht, einer den Wirkstoff enthaltenden Matrix und einem Haftkleber, der mit einer wiederablösbaren Schutz schicht abgedeckt ist, beschrieben. Die Herstellung von Ma trix und Haftkleber erfolgen in technologisch sehr aufwen digen Arbeitsvorgängen durch Homogenisieren, Entgasen, Be schichten, Trocknen und Vereinzeln. In einer Ausführungs form muß die Rückschicht sogar mit einem Haftkleber be schichtet werde, was einen weiteten Arbeitsgang bedingt. Das Zusammenfügen der einzelnen Teile erfolgt in einem se paraten Arbeitsgang. Die Herstellung des Pflasters ist also insgesamt sehr aufwendig und kompliziert.In WO 87/07138 is an estradiol patch with a Backing layer, a matrix containing the active ingredient and a pressure sensitive adhesive that comes with a removable protection layer is covered. The production of Ma Trix and pressure sensitive adhesive are technologically very complex end processes by homogenizing, degassing, loading layering, drying and separating. In an execution form the backing must even be with a pressure sensitive adhesive stratified, which requires an extended work step. The individual parts are put together in one se separate operation. So the manufacture of the patch is overall very complex and complicated.
Aus der US 4 624 665 sind Systeme bekannt, die im Reservoir den Wirkstoff in mikroverkapselter Form enthalten. Das Re servoir ist eingebettet zwischen Rückschicht und einer Mem bran. Der äußere Rand des Systems ist mit einem Haftkleber ausgerüstet. Der Aufbau und die Herstellung dieses Systems ist sehr kompliziert, da der Wirk stoff mikroverkapselt und in einer flüssigen Phase homogen verteilt werden muß, die dann in weiteren Arbeitsgängen zwischen Rückschicht und Membran eingebettet wird. Zusätzlich muß das System dann mit einem klebenden Rand versehen und mit einer Schutzschicht abgedeckt werden.Systems are known from US Pat. No. 4,624,665 which are in the reservoir contain the active ingredient in microencapsulated form. The Re servoir is embedded between the backing and a mem bran. The outer edge of the system is equipped with a pressure sensitive adhesive. The The construction and manufacture of this system is very complicated because of the effect microencapsulated and homogeneously distributed in a liquid phase must then in further operations between the backing layer and membrane is embedded. In addition, the system must then have an adhesive edge provided and covered with a protective layer.
Es sind weiterhin aus der EP 0 186 019 Wirkstoffpflaster bekannt, bei denen einer Kautschuk/Klebharzmasse in Wasser quellbare Polymere zugesetzt sind und aus denen u. a. auch Steroidhormone, z. B. Estradiol, freigesetzt wer den können. Durch den Zusatz von quellbaren Polymeren wird eine Erhöhung der Freisetzungsrate bewirkt. Es hat sich jedoch gezeigt, daß die Freisetzung von Estradiol aus diesen Wirkstoffpflastern viel zu gering ist und nicht den the rapeutischen Erfordernissen entspricht.Active ingredient plasters are also known from EP 0 186 019, in which added to a rubber / adhesive resin swellable polymer in water are and from which u. a. also steroid hormones, e.g. B. estradiol, who released that can. By adding swellable polymers an increase of the release rate. However, it has been shown that the release of estradiol from these patches is too low and not the corresponds to therapeutic requirements.
In der DE-OS 20 06 696 ist ein Pflaster oder ein Haftverband mit Systemwir kung beschrieben, bei dem empfängnisverhütende Substanzen in der Kleb stoffkomponente oder dem Klebstoffilm eingearbeitet sind. Der Klebstoffilm kann ein Acrylat sein.In DE-OS 20 06 696 there is a plaster or adhesive dressing with a system kung, in which contraceptive substances in the adhesive component or the adhesive film are incorporated. The adhesive film can be an acrylate.
Es ist somit Aufgabe der vorliegenden Erfindung, die oben aufgeführten Nach teile zu vermeiden und ein stabiles, das heißt rekristallisationsfreies oestrogen- und/oder gestagenhaltiges Pflaster zur Verfügung zu stellen, dessen Freiset zung sich durch Lagerung nicht verändert.It is therefore an object of the present invention, the above listed avoid parts and a stable, i.e. recrystallization-free estrogen and / or to provide progestin-containing plaster, the release set storage does not change.
Überraschend hat sich gezeigt, daß die Aufgabe durch einen oestrogen- und/ oder gestagenhaltigen Haftkleber, der Wollwachs oder Bestandteile davon und Zinkoxid enthält, gelöst wird.Surprisingly, it has been shown that the task is caused by an estrogen and / or progestogen-containing pressure sensitive adhesive, the wool wax or parts thereof and Contains zinc oxide is dissolved.
Die oben gestellte Aufgabe wird daher durch ein wirkstoffhaltiges Pflaster ge mäß Hauptanspruch gelöst. Die Unteransprüche betreffen besonders bevor zugte Ausführungsformen des Erfindungsgegenstandes. The above task is therefore ge by an active substance-containing patch solved according to main claim. The sub-claims relate particularly before preferred embodiments of the subject matter of the invention.
Wollwachs ist als pharmazeutischer Rohstoff bekannt und als solcher in den Pharmakopoen beschrieben. Es wird verwendet aufgrund seines Liberations vermögens für Wirkstoffe, seiner Hautfreundlichkeit und seines Wasserauf nahmevermögens. Beispielsweise ist Wollwachs, zusammen mit Zinkoxid, auch Bestandteil eines für die Herstellung von medizinischen Pflastern geeigneten Haftklebers, der in der DD 251 567 A1 beschrieben wird. Dabei werden die Eignung des Wollwachses als Weichmacher und seine Schweißaufnahmefä higkeit als vorteilhaft genannt.Wool wax is known as a pharmaceutical raw material and as such in the Pharmacopoeia described. It is used because of its liberalization ability for active ingredients, its skin friendliness and its water level capacity. For example, wool wax, along with zinc oxide, is also Part of a suitable for the production of medical plasters Pressure sensitive adhesive, which is described in DD 251 567 A1. The Suitability of wool wax as a plasticizer and its sweat absorption ability mentioned as advantageous.
Auch Zinkoxid ist in den Pharmakopoen beschrieben. Zinkoxid wirkt als mildes Desinfiziens und entzündungswidrig, darüber hinaus reagiert es schwach alka lisch. Ferner wird es bei Arzneizubereitungen, auch bei Wirkstoffpflastern, als Füllstoff eingesetzt. Aus der EP 0 787 488 A1 ist ein oestrogen- und gestagen haltiges Transdermalpflaster bekannt, welches auch Zinkoxid als Füllstoff ent halten kann.Zinc oxide is also described in the pharmacopoeias. Zinc oxide acts as a mild one Disinfectant and anti-inflammatory, in addition it reacts weakly alkali lish. It is also used in pharmaceutical preparations, including active substance plasters Filler used. EP 0 787 488 A1 describes an estrogen and gestagen containing transdermal patches known, which also ent zinc oxide as a filler can hold.
Das erfindungsgemäße wirkstoffhaltige Pflaster kann für kosmetische sowie therapeutische Zwecke in der Human- und Veterinärmedizin verwendet wer den.The active ingredient-containing plaster can be used for cosmetic as well therapeutic purposes used in human and veterinary medicine the.
Das rekristallisationsfreie oestrogen- und/oder gestagenhaltige Pflaster mit ausreichender Wirkstofffreisetzung enthält im Reservoir Estradiol und seine pharmazeutisch unbedenklichen Derivate allein oder in Kombination mit Gestagenen in einer Konzentration von insgesamt 1-20 Gew.-%, bezogen auf die Gesamtheit der Reservoirbestandteile, und zwar in einem molaren Verhält nis von 1 : 1 bis 1 : 10.The recrystallization-free patch containing estrogen and / or gestagen sufficient drug release contains estradiol and its in the reservoir pharmaceutically acceptable derivatives alone or in combination with Gestagens in a total concentration of 1-20% by weight, based on the entirety of the reservoir components, in a molar ratio nis from 1: 1 to 1:10.
Das estradiolhaltige Reservoir kann mindestens einen Bestandteil der Gruppe enthalten, welche Alterungsschutzmittel, Weichmacher, Antioxidantien und Ab sorptionsverbesserer umfaßt. Geeignete Weichmacher sind dem Fachmann bekannt und beispielsweise in der DE 37 43 946 beschrieben. Das estradiol haltige Reservoir enthält üblicherweise Weichmacher in einem Anteil bis zu 5 Gew.-%.The estradiol-containing reservoir can be at least one component of the group contain which anti-aging agents, plasticizers, antioxidants and Ab sorption enhancer comprises. Suitable plasticizers are known to the person skilled in the art known and described for example in DE 37 43 946. The estradiol containing reservoir usually contains plasticizers in a proportion up to 5 % By weight.
Weiterhin sind im wirkstoffhaltigen Reservoir auch Alterungsschutzmittel in ei ner Konzentration bis zu 1 Gew.-% enthalten. Diese sind dem Fachmann bekannt und z. B. in der DE 37 43 946 beschrieben.Furthermore, anti-aging agents are also present in the active ingredient-containing reservoir concentration up to 1% by weight contain. These are known to the expert and z. B. in the DE 37 43 946.
Die Materialien für die undurchlässige Rückschicht und die wiederablösbare Schutzschicht sind dem Fachmann ebenso be kannt.The materials for the impermeable backing and the Removable protective layers are also known to the person skilled in the art knows.
Das estradiolhaltige Reservoir kann aus Lösung, aus Disper sion und auch aus der Schmelze erzeugt werden.The estradiol-containing reservoir can be from solution, from disper sion and also be generated from the melt.
Das Reservoir kann aus mehreren Schichten bestehen.The reservoir can consist of several layers.
Für den Fall, daß das Reservoir keine ausreichende Eigen klebrigkeit zur Haut aufweist, kann dieses mit einer zu sätzlichen wirkstofffreien haftklebenden Schicht oder mit einem umlaufenden haftklebenden Rand versehen werden. Auf diese Weise ist gewährleistet, daß das transdermale Pfla ster über den gesamten Applikationszeitraum auf der Haut haftet.In the event that the reservoir is insufficient own has stickiness to the skin, this can with a too additional active ingredient-free pressure-sensitive adhesive layer or with be provided with an all-round adhesive border. On this ensures that the transdermal Pfla over the entire application period on the skin is liable.
Ein besonders bevorzugter Aufbau des transdermalen estra diolhaltigen Pflasters ist ein Matrix-System, bei dem be kanntlich die Matrix die Steuerung für die Wirkstofffrei setzung übernimmt und dem √t-Gesetz nach Higuchi gehorcht. Das bedeutet jedoch nicht, daß nicht in besonderen Fällen auch ein Membran-System von Vorteil ist. Hierbei ist zwi schen Reservoir und Haftkleberschicht eine die Wirkstoff freisetzung steuernde Membran angebracht.A particularly preferred structure of the transdermal estra diol-containing patch is a matrix system in which be The matrix is known to be the control for the active ingredient-free takes over and obeys the √t law according to Higuchi. However, that does not mean that not in special cases a membrane system is also an advantage. Here is between The reservoir and PSA layer are the active ingredient release control membrane attached.
Die Dicke des transdermalen Pflasters richtet sich nach den therapeutischen Erfordernissen und kann entsprechend ange paßt werden. Sie liegt üblicherweise im Bereich von 0,03- 0,6 mm.The thickness of the transdermal patch depends on the therapeutic requirements and can accordingly be fit. It is usually in the range of 0.03- 0.6 mm.
Die Erfindung wird nachfolgend anhand von Ausführungsbei spielen erläutert.The invention is explained below with reference to exemplary embodiments play explained.
Die Herstellung erfolgt wie unter Beispiel 1 beschrieben, jedoch mit in Tabelle 1 (Herstellformel) angegebenen Roh stoffmengen.The preparation is carried out as described in Example 1, however with raw specified in Table 1 (manufacturing formula) quantities of substance.
Zur Messung der Humanhautpenetration wird die Haut in die Franz-Zelle eingespannt. Auf die Haut wird ein oestrogen- und/oder gestagenhaltiges Pflaster mit einer Fläche von 1,539 cm2 aufgeklebt und die Wirkstofffreisetzung bei 37°C (Akzeptormedium: 0,9%ige Kochsalzlösung + 0,1% NaN3) ge messen.To measure human skin penetration, the skin is clamped in the Franz cell. An estrogen- and / or gestagen-containing patch with an area of 1.539 cm 2 is applied to the skin and the active substance release is measured at 37 ° C. (acceptor medium: 0.9% saline + 0.1% NaN 3 ).
Die Prüfung auf Rekristallisationserscheinung wird visuell im Gegenlicht durchgeführt.The check for recrystallization is visual performed against the light.
Die Ergebnisse sind in Tabelle 2 dargestellt.The results are shown in Table 2.
Wie die Tabelle zeigt, erhält man bei dem erfindungsgemäßen Pflaster eine deutlich bessere Penetration durch die Human haut gegenüber dem Vergleichsprodukt. Parallel dazu kann festgestellt werden, daß die Rekristallisation bei den er findungsgemäßen Beispielen völlig unterbleibt.As the table shows, one obtains with the invention Patch a significantly better penetration by the human skin compared to the comparative product. In parallel can found that the recrystallization at which he Examples according to the invention are completely omitted.
Claims (14)
Priority Applications (20)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19834007A DE19834007C1 (en) | 1998-07-29 | 1998-07-29 | Estradiol-containing patch for the transdermal application of hormones and its use |
AU51607/99A AU758107B2 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
JP2000561986A JP2002521427A (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
CA002338859A CA2338859C (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
TR2001/00289T TR200100289T2 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal hormone administration |
DE59909189T DE59909189D1 (en) | 1998-07-29 | 1999-07-16 | Patches suitable for the transdermal application of estradiol and wool wax or components thereof and zinc oxide |
CNB998088528A CN1172661C (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
AT99936555T ATE264097T1 (en) | 1998-07-29 | 1999-07-16 | PLASTERS SUITABLE FOR TRANSDERMAL APPLICATION OF ESTRADIOL AND CONTAIN WOOL WAX OR COMPONENTS THEREOF AND ZINC OXIDE |
PL99345695A PL194102B1 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
US09/744,711 US6531149B1 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal application of hormones |
PCT/EP1999/005085 WO2000006131A1 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal administration of hormones |
IL14103399A IL141033A0 (en) | 1998-07-29 | 1999-07-16 | Estradiol containing patch for transdermal administration of hormones |
EP99936555A EP1100477B1 (en) | 1998-07-29 | 1999-07-16 | Patch comprising wool fat or its components and zinc oxide, suitable for the transdermal administration of estradiol |
BR9912687-7A BR9912687A (en) | 1998-07-29 | 1999-07-16 | Plaster containing an active substance and its use |
ES99936555T ES2220093T3 (en) | 1998-07-29 | 1999-07-16 | PATCH CONTAINING LANOLIN, OR ITS COMPONENTS, AND CINC OXIDE, FOR THE TRANSDERMIC ADMINISTRATION OF ESTRADIOL. |
KR1020017001313A KR100559089B1 (en) | 1998-07-29 | 1999-07-16 | Estradiol-containing patch for transdermal application of hormones |
TW088112440A TW542726B (en) | 1998-07-29 | 1999-07-22 | Estradiol-containing patch for transdermal application of hormones |
ARP990103732A AR021459A1 (en) | 1998-07-29 | 1999-07-28 | PATCH CONTAINING ESTRADIOL FOR THE PERCUTANEOUS APPLICATION OF HORMONES. |
IL141033A IL141033A (en) | 1998-07-29 | 2001-01-23 | Estradiol-containing patch for transdermal administration of hormones |
ZA200100719A ZA200100719B (en) | 1998-07-29 | 2001-01-25 | Estradiol-containing patch for transdermal administration of hormones. |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19834007A DE19834007C1 (en) | 1998-07-29 | 1998-07-29 | Estradiol-containing patch for the transdermal application of hormones and its use |
Publications (1)
Publication Number | Publication Date |
---|---|
DE19834007C1 true DE19834007C1 (en) | 2000-02-24 |
Family
ID=7875613
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19834007A Expired - Fee Related DE19834007C1 (en) | 1998-07-29 | 1998-07-29 | Estradiol-containing patch for the transdermal application of hormones and its use |
DE59909189T Expired - Lifetime DE59909189D1 (en) | 1998-07-29 | 1999-07-16 | Patches suitable for the transdermal application of estradiol and wool wax or components thereof and zinc oxide |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE59909189T Expired - Lifetime DE59909189D1 (en) | 1998-07-29 | 1999-07-16 | Patches suitable for the transdermal application of estradiol and wool wax or components thereof and zinc oxide |
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US (1) | US6531149B1 (en) |
EP (1) | EP1100477B1 (en) |
JP (1) | JP2002521427A (en) |
KR (1) | KR100559089B1 (en) |
CN (1) | CN1172661C (en) |
AR (1) | AR021459A1 (en) |
AT (1) | ATE264097T1 (en) |
AU (1) | AU758107B2 (en) |
BR (1) | BR9912687A (en) |
CA (1) | CA2338859C (en) |
DE (2) | DE19834007C1 (en) |
ES (1) | ES2220093T3 (en) |
IL (2) | IL141033A0 (en) |
PL (1) | PL194102B1 (en) |
TR (1) | TR200100289T2 (en) |
TW (1) | TW542726B (en) |
WO (1) | WO2000006131A1 (en) |
ZA (1) | ZA200100719B (en) |
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US9301920B2 (en) | 2012-06-18 | 2016-04-05 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
ES2885523T3 (en) | 2011-11-23 | 2021-12-14 | Therapeuticsmd Inc | Natural combination hormone replacement formulations and therapies |
US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US20130338122A1 (en) | 2012-06-18 | 2013-12-19 | Therapeuticsmd, Inc. | Transdermal hormone replacement therapies |
US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
AU2015264003A1 (en) | 2014-05-22 | 2016-11-17 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
AU2017239645A1 (en) | 2016-04-01 | 2018-10-18 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical composition |
US11633405B2 (en) | 2020-02-07 | 2023-04-25 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical formulations |
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-
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- 1999-07-16 EP EP99936555A patent/EP1100477B1/en not_active Expired - Lifetime
- 1999-07-16 CA CA002338859A patent/CA2338859C/en not_active Expired - Fee Related
- 1999-07-16 CN CNB998088528A patent/CN1172661C/en not_active Expired - Fee Related
- 1999-07-16 IL IL14103399A patent/IL141033A0/en unknown
- 1999-07-16 DE DE59909189T patent/DE59909189D1/en not_active Expired - Lifetime
- 1999-07-16 AU AU51607/99A patent/AU758107B2/en not_active Ceased
- 1999-07-16 AT AT99936555T patent/ATE264097T1/en not_active IP Right Cessation
- 1999-07-16 JP JP2000561986A patent/JP2002521427A/en active Pending
- 1999-07-16 ES ES99936555T patent/ES2220093T3/en not_active Expired - Lifetime
- 1999-07-16 PL PL99345695A patent/PL194102B1/en not_active IP Right Cessation
- 1999-07-16 US US09/744,711 patent/US6531149B1/en not_active Expired - Fee Related
- 1999-07-16 WO PCT/EP1999/005085 patent/WO2000006131A1/en active IP Right Grant
- 1999-07-16 TR TR2001/00289T patent/TR200100289T2/en unknown
- 1999-07-16 KR KR1020017001313A patent/KR100559089B1/en not_active IP Right Cessation
- 1999-07-22 TW TW088112440A patent/TW542726B/en not_active IP Right Cessation
- 1999-07-28 AR ARP990103732A patent/AR021459A1/en active IP Right Grant
-
2001
- 2001-01-23 IL IL141033A patent/IL141033A/en not_active IP Right Cessation
- 2001-01-25 ZA ZA200100719A patent/ZA200100719B/en unknown
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EP0787488A1 (en) * | 1994-11-18 | 1997-08-06 | Hisamitsu Pharmaceutical Co., Inc. | Percutaneously absorbable patch |
Also Published As
Publication number | Publication date |
---|---|
AU758107B2 (en) | 2003-03-13 |
EP1100477B1 (en) | 2004-04-14 |
US6531149B1 (en) | 2003-03-11 |
AU5160799A (en) | 2000-02-21 |
TR200100289T2 (en) | 2001-07-23 |
PL194102B1 (en) | 2007-04-30 |
TW542726B (en) | 2003-07-21 |
WO2000006131A1 (en) | 2000-02-10 |
ZA200100719B (en) | 2002-06-14 |
DE59909189D1 (en) | 2004-05-19 |
CA2338859C (en) | 2007-09-18 |
IL141033A0 (en) | 2002-02-10 |
EP1100477A1 (en) | 2001-05-23 |
CN1310614A (en) | 2001-08-29 |
JP2002521427A (en) | 2002-07-16 |
KR20010079571A (en) | 2001-08-22 |
IL141033A (en) | 2009-06-15 |
BR9912687A (en) | 2001-06-05 |
CA2338859A1 (en) | 2000-02-10 |
KR100559089B1 (en) | 2006-03-13 |
ES2220093T3 (en) | 2004-12-01 |
ATE264097T1 (en) | 2004-04-15 |
CN1172661C (en) | 2004-10-27 |
PL345695A1 (en) | 2002-01-02 |
AR021459A1 (en) | 2002-07-24 |
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Legal Events
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8100 | Publication of patent without earlier publication of application | ||
D1 | Grant (no unexamined application published) patent law 81 | ||
8327 | Change in the person/name/address of the patent owner |
Owner name: LTS LOHMANN THERAPIE-SYSTEME AG, 56626 ANDERNACH, |
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8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee | ||
R119 | Application deemed withdrawn, or ip right lapsed, due to non-payment of renewal fee |
Effective date: 20110201 |